The Immunology Core I was originally established as the Molecular Immunology Core with three subcores focused on humoral immunity, cellular immunity, and flow-based assays. The mission of this Core is to develop, refine, and provide by training and technology-transfer state-of-the-art immunological assays to evaluate and quantify humoral and cellular responses to support NIH-sponsored AIDS research and training. The assays, reagents, and training offered by the Core are designed to support basic, clinical, and translational research in the prevention, detection, and treatment of HIV infection and AIDS. During the last five years, this Immunology Core has significantly increased its user base, with an overall 3.9-fold increase in total users from 21 to 82, and a 5.4-fold increase in support of local users (60% of total) and a 2.8-fold increase in non-local users (40% of total). Since 2002, the Immunology Core has continuously worked to expand its impact by focusing on the training of investigators in the use of the Core's technologies. As an example of these activities, we developed a hands-on workshop entitled "Research ELISA Assays: The Practical Guide" in Nairobi, Kenya, February 14-25, 2005. Highlights of research progress during the last five years have included studies on HIV Envelope tropism, Envelope variation and its relationship to the development of neutralizing antibodies (NAbs), the role of antibodies in perinatal transmission in nonhuman primates, examination of the role of IgG with ADCC activity in newborn macaques, hepatitis C-specific T cell responses and phenotypic analysis of liver NK T cells, gamma-delta T cell involvement in the viral immune control of chronic human herpesvirus-8 (HHV8) infection, epitope-specific T cell proliferation in HIV-infected subjects with long-term nonprogression, detailed examination of T cell responses to HIV-2, novel scaffold approaches to present HIV Envelope epitopes as vaccines, and support of translational studies. Over the next five years, we propose: (1) continuous development of state-of-the art assays within a more streamlined organization with two cores located in two, rather than three, locations;(2) the inclusion of a new Core Manager;(3) a redistributed budget to support a higher level of personnel to provide expanded services to a wider group of users;(4) linkages to a new Protein Core at the Seattle Biomedical Research Institute to obtain materials in a more cost-effective manner;and (5) a stronger focus on outreach, with training sessions for individual investigators and technical workshops for groups requesting services to transfer technology and reagents.